Molecular and functional characterization of melanocyte subpopulations in adult human epidermis based on single-cell RNA sequencing

Melanocytes are considered cells-of-origin of melanomas. Because heterogeneity within melanocyte subpopulations between developmental lineages (e.g. progenitors or progenies) or anatomical areas (e.g. hairy vs glabrous skin) would be the base of inter-tumor heterogeneity in melanoma subtypes, refined characterization of melanocyte lineages should facilitate understanding development of melanomas.Here we genetically, phenotypically and functionally studied heterogeneity in normal epidermal melanocytes in human hairy (breast) skin utilizing single cell RNA-seq. Four epidermal melanocyte subpopulations were newly determined by single cell molecular profiling. Within them we identified one subpopulation with transcriptomes corresponding to the activated progenitor/precursor melanocytes both in the inter-follicular epidermis and the hair follicle. Interestingly this subpopulation was augmented in tanned than in less tanned areas of the fresh human skin and showed enhanced clonogenicity, ribosome biogenesis and radio-resistance against ultraviolet B (UVB) in vitro, indicating association with melanomagenesis in the context of sun-exposure.